In:
Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 205, No. 2 ( 2024-06), p. 267-279
Abstract:
Previous studies have reported the benefit of dual HER2-targeting combined to neoadjuvant chemotherapy in HER2-amplified breast cancer (HER2 + BC). Moreover, besides the cardiac toxicity following their association to Trastuzumab, anthracyclines chemotherapy may not profit all patients. The NeoTOP study was designed to evaluate the complementary action of Trastuzumab and Pertuzumab, and the relevance of an anthracycline-based regimen according to TOP2A amplification status. Methods Open-label, multicentre, phase II study. Eligible patients were aged ≥ 18 with untreated, operable, histologically confirmed HER2 + BC. After centralized review of TOP2A status, TOP2A-amplified (TOP2A+) patients received FEC100 for 3 cycles then 3 cycles of Trastuzumab (8 mg/kg then 6 mg/kg), Pertuzumab (840 mg/kg then 420 mg/kg), and Docetaxel (75mg/m 2 then 100mg/m 2 ). TOP2A-not amplified (TOP2A-) patients received 6 cycles of Docetaxel (75mg/m 2 ) and Carboplatin (target AUC 6 mg/ml/min) plus Trastuzumab and Pertuzumab. Primary endpoint was pathological Complete Response (pCR) using Chevallier’s classification. Secondary endpoints included pCR (Sataloff), Progression-Free Survival (PFS), Overall Survival (OS), and toxicity. Results Out of 74 patients, 41 and 33 were allocated to the TOP2A + and TOP2A- groups respectively. pCR rates (Chevallier) were 74.4% (95%CI: 58.9–85.4) vs. 71.9% (95%CI: 54.6–84.4) in the TOP2A + vs. TOP2A- groups. pCR rates (Sataloff), 5-year PFS and OS were 70.6% (95%CI: 53.8–83.2) vs. 61.5% (95%CI: 42.5–77.6), 82.4% (95%CI: 62.2–93.6) vs. 100% (95%CI: 74.1–100), and 90% (95%CI: 69.8–98.3) vs. 100% (95%CI: 74.1–100). Toxicity profile was consistent with previous reports. Conclusion Our results showed high pCR rates with Trastuzumab and Pertuzumab associated to chemotherapy. They were similar in TOP2A + and TOP2A- groups and the current role of neoadjuvant anthracycline-based chemotherapy remains questioned. Trial registration number NCT02339532 (registered on 14/12/14).
Type of Medium:
Online Resource
ISSN:
0167-6806
,
1573-7217
DOI:
10.1007/s10549-024-07285-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2024
detail.hit.zdb_id:
604563-7
detail.hit.zdb_id:
2004077-5
Permalink